Nonsecretory and Light Chain Escape in Patients With Multiple Myeloma

Multiple myeloma secretes a monoclonal protein, either as intact immunoglobulin molecule, or light chain. These paraproteins are used as tumor markers to monitor disease activity. Among 791 patients, multiple myeloma lost the paraprotein production (“nonsecretory escape”) or switched it from the intact immunoglobulin to its light chain only (“light chain escape”) in 3.5% of cases. This phenomenon was associated with more aggressive clinical features and worse clinical outcome. Background: Multiple myeloma (MM) is characterized by the secretion of monoclonal protein by malignant plasma cells in the vast majority of cases. We identified and analyzed patterns of disease relapse and progression associated with disappearance of the paraprotein (“nonsecretory [NS] escape”), or conversion from production of intact Ig molecule to its associated light chain (“LC escape”). Patients and Methods: We retrospectively reviewed medical records and a database of 791 consecutive patients with symptomatic MM. Results: Twenty-eight (3.5%) patients had disease evolution associated with either NS (n = 13) or LC (n = 15) escape. The event occurred at a median of 37 months (range, 3-156 months) after the diagnosis of MM, and after a median of 3 chemotherapy regimens (range, 1-8 regimens). Presence of extramedullary disease at progression was detected in 8 (29%) patients. Sensitivity to chemotherapy before and after escape was present in 21 (75%) and 14 (50%) patients, respectively. After a median follow-up of 55 months, 19 (68%) patients died, and progressive MM was the cause of death in 18 patients. The median overall survival after escape was 20 months (95% confidence interval, 9-25 months), and no significant difference was found between the NS and LC groups (P =.44). The median overall survival after diagnosis of MM was worse in patients with NS/LC escape than in those without escape (52 vs. 94 months; P =.018). Conclusions: Our study describes the largest series of NS and LC escape in MM to date. The development of this phenomenon is associated with more aggressive clinical features, frequent resistance to chemotherapy, and worse clinical outcome.